The goal of the proposed research is to better understand the process of ribosome biogenesis. Biosynthesis of the yeast Saccharomyces cerevisiae ribosome requires the coordinate regulation of -450 ribosomal RNA (rRNA) genes and 137 ribosomal proteins (RPs). In addition several classes of transacting factors are required to properly synthesize a mature ribosome. These factors carry out assembly and maturation activities in pre-ribonucleoprotein (RNP) particles along with the RPs and rRNAs. Although the identity of trans-acting factors is known, the precise timing of entry and exit of the processing pathway and the ordered assembly of ribosomal proteins is poorly understood. This research will employ genetic and biochemical approaches to identify and characterize specific pre-RNP particles that are involved in biogenesis of the 60S ribosomal subunit. Hopefully, this work will allow us to generate a map of the ordered assembly pathway for the trans-acting factors that function in biogenesis of the 60S subunit by elucidating the formation, rearrangement and maturation of specific protein-rRNA complexes. This research has implications to cancer biology, as the ribosome has an important role in cell proliferation and growth Furthermore, genetic defects in nucleolar proteins, ribosomal proteins and rRNAs have been linked to a number of diseases that arise as a result of improper assembly and biogenesis of ribosomes.